An optically active 1-(2-trifluoromethylphenyl)ethanol is important as an intermediate for medicines (cf. Patent Document 1). Optically active 1-phenyl ethanols can be produced by chemical or biological asymmetric reduction of corresponding acetophenones. It is however difficult only by such asymmetric reduction reaction that the resulting reaction product satisfies the level of optical purity required for use as an intermediate for medicines. In order to obtain the product of desired optical purity, there is a need to perform purification such as conversion of the reaction product to a derivative thereof and kinetic resolution of the reaction product in combination with the asymmetric reduction reaction. The above purification operation results in not only a deterioration of productivity due to an increase in the number of operation steps but also a decrease of total yield and an increase of waste. It is thus important in this field to find out how to improve the optical purity of the asymmetric reduction product efficiently by simple operation.
There is no report of any purification method by which the optical purity of the target compound of the present invention, an optically active 1-(2-trifluoromethylphenyl)ethanol, can be improved efficiently by simple operation.
A purification method of a similar compound, an optically active 1-(3,5-bistrifluoromethylphenyl)ethanol, is already reported (cf. Non Patent Document 1). As the optically active 1-(3,5-bistrifluoromethylphenyl)ethanol gets preferentially deposited in racemic crystal form by recrystallization, it is impossible to efficiently improve the optical purity of the 1-(3,5-bistrifluoromethylphenyl)ethanol by recrystallization. The optical purity of the optically active 1-(3,5-bistrifluoromethylphenyl)ethanol is thus improved by recrystallizing a complex of the optically active 1-(3,5-bistrifluoromethylphenyl)ethanol and DABCO (1,4-diazabicyclo[2.2.2]octane) (1-(3,5-bistrifluoromethylphenyl)ethanol: DABCO=2:1). In this method, however, it is necessary to use 0.5 equivalent weight of the relatively expensive DABCO and to recover the optically active 1-(3,5-bistrifluoromethylphenyl)ethanol from the complex after the recrystallization.
Further, the present applicant has disclosed that it is not possible to improve the optical purity of either of an optically active 1-(3-trifluoromethylphenyl)ethanol and an optically active 1-(4-trifluoromethylphenyl)ethanol efficiently only by recrystallization. The optically active 1-(3-trifluoromethylphenyl)ethanol does not get favorably deposited in crystal form by recrystallization (cf. Reference examples 3 to 6 in TABLE 3). The optically active 1-(4-trifluoromethylphenyl)ethanol cannot be obtained with high optical purity by recrystallization (cf. Reference examples 7 to 10 in TABLE 4).
On the other hand, the present applicant has disclosed a method for producing the target compound of the present invention, an optically active 1-(2-trifluoromethylphenyl)ethanol, by optical resolution of a corresponding racemic phthalic half ester with an optically active 1-phenylethylamine (cf. Patent Document 2).
Patent Document 1: International Publication No. 2007/030359
Patent Document 2: Japanese Laid-Open Patent Publication No. 2007-106702
Non Patent Document 1: Tetrahedron: Asymmetry (U.K.), 2003, Vol. 14, P. 3581-3587